Conventionally, a surface plasmon resonance sensor, for instance, has been used as an affinity sensor for detecting whether or not there is adsorption or coupling of substances, such as whether or not there is adsorption or coupling of an antigen in an antigen-antibody reaction.
In general, the surface plasmon resonance sensor comprises a detecting unit including a surface in contact with a test sample, means for light irradiation to the detecting unit and photo-detecting means for detecting reflected light from the detecting unit. The detecting unit comprises a prism and a metal film formed on a surface of the prism and contacting the sample. The light irradiation means includes a light source and an optical system which are placed to be able to acquire various angles of incidence of a light beam against an interface between the prism and the metal film. The photo-detecting means detects intensity of total reflected light reflected off the interface between the prism and the metal film as to each of the various angles of incidence by incidence of the light beam on the detecting unit.
However, the sensor has problems that its configuration becomes complicated because the detecting unit requires the prism as its component, and the detecting unit cannot be placed in a little place where the prism can hardly be placed.
The metal film formed on one surface of the prism in the detecting unit is generally formed by using a vacuum evaporation method. For that reason, a vacuum evaporator requires a special structure for vacuum-evaporating the metal film on a predetermined surface of the prism.
Development is underway as to various methods which utilize surface plasmon resonance using an attenuated total reflection method as above, and there are already commercialized products. As described above, however, it is difficult to miniaturize the sensor having the above configuration because the configuration of the optical system becomes complicated and restrictions on placement are strict.
As for these problems, there are proposals of various devices of simple configurations which are capable of detecting. The following are known for instance.
(a) Japanese Patent Application Laid-Open No. 2000-356587 discloses a sensor having a structure in which a metal structure is fixed like a film on the surface of a substrate. In this case, it detects adsorption or deposition of substances on the metal structure by emitting light to the substrate and measuring absorbance of a measuring beam transmitted through the metal structure on the backside of the substrate. This allowed the detecting by a simple device configuration with no need of the prism as a component. The publication also proposes a sensor utilizing an optical fiber as another example of the simple configuration.
(b) Applied Physics 72, 1541 (2003) reports a small sensor having practical-level sensitivity which has the metal structure deposited on an end face (effective diameter 50 μm) of the optical fiber.
(c) Japanese Patent Application Laid-Open No. 2004-191110 discloses a sensor which utilizes plasmon resonance having covered a fiber side face with a gold thin film.
The above (a) and (b) utilize localized plasmon resonance of the metal structure and (c) utilizes surface plasmon resonance of a metal thin film so as to allow highly sensitive detecting.
Here, in the configuration, the measuring beam is transmitted through one of particles placed with spacing just once and influenced by the plasmon resonance of only a single metal structure on the transmission thereof. The above (c) has the configuration in which the beam is reflected off the gold thin film on the fiber side face to be influenced by the plasmon resonance. In all the cases of the sensors of (a), (b) and (c), the light irradiation means is configured to have the measuring beam incident at an angle on a surface constituted by an arranged metal structure (thin film) or a metal thin film surface. According to this configuration, there is no concept that the beam transmits through the metal structure plural times or the beam effectively passes through only the metal structure so that interaction between the beam and the metal is reduced. For that reason, the ratio of a signal (change in light volume) light volume obtained by adhesion of substances to the metal structure obtained against the light volume of the beam incident on the substrate is small.
Japanese Patent Application Laid-Open No. 2005-283556 discloses an element for recognizing a target substance in a sample. The element has plural particles including metallic elements at least on the surface of a minute structure, and detects a change in properties of the particles based on the sum of the light outputted from the plural particles against irradiation of detecting beams. The detecting method disclosed by the publication is characterized in that high signal intensity can be obtained because signals from the plural particles are comprehensively detected. However, all the detecting beams entering all the sensors do not pass through the particles since a part of the detecting beams passes through a columnar portion of the minute structure or directly passes inside a flow path. Therefore, there remains a factor for lowering an S/N ratio.
In the above-mentioned detecting method using the sensor, it is required to improve detecting accuracy as to a phenomenon of which S/N ratio is small signal beam for detecting is small against background light). For that reason, it required a high-performance signal separation technique of a high dynamic range or a technique for separating the background light.
Under a condition that concentration of a target substance is lean, an area in which the target substance was coupled to a trapping body substance was narrow against a trapping body fixed on the element so that a signal was submerged and detecting of minute amounts became difficult.